Project Summary As of April 2nd, 2020, the total number of confirmed COVID-19 cases in the United States exceeds 200,000 and is escalating rapidly. The Institute for Health Metrics and Evaluation projects that COVID-19 cases in the US will surge mid-to-late April, leading to hospitalization of as many as 2.4 to 21 million people; numbers that will overwhelm the US healthcare system. Confronted with a pandemic that threatens the lives of millions, with no vaccines or effective drugs in sight, the clinical community is evaluating convalescent plasma/serum as an urgent countermeasure to thwart new infections and ameliorate COVID-19 related morbidity and mortality. The number of recovered individuals in the US is at present 8,500 and as these numbers continue to grow, so will the availability of plasma rich in SARS antibodies from recovered donors. Infusion of convalescent plasma prophylactically could immunize health care workers against nascent infections and therapeutic infusion could decrease the likelihood of severe disease in infected patients. As a result, several academic medical centers across the nation have begun trials to use convalescent plasma to treat patients, with many hospitals in New York starting treatments this week. Given the potential for broad implementation of convalescent plasma therapy in the US in the coming weeks there is an urgent need to evaluate the prophylactic and therapeutic ability of convalescent plasma as a stand- alone treatment against COVID-19 using an animal model where timing and dose of infection can be controlled; immunopathology to organ systems can be rigorously assessed by collection of tissue biopsies, and where re- challenge experiments can critically evaluate long-term impact of convalescent plasma therapy on protective immunity. The goals of this study are to determine if human plasma from convalescent COVID 19 patients prevents primary infection, decreases viremia in the event of breakthrough infections, and alters susceptibility to a secondary challenge. We are collaborating with UCD Health clinicians who are conducting human trial titled: Convalescent Plasma to Stem Coronavirus. We will use an aliquot of the same plasma used in human trials for our rhesus studies. We will inoculate rhesus monkeys with the Davis SARS-CoV-2 isolate (2019-nCoV/USA- CA9/2020; GenBank: MT118835.1) to address these questions within a timeline of 30 days. Urgency and relevance to Emergency Guide Notice: Our animal studies will critically inform efficacy in the short term and potential risks in the long term of convalescent plasma therapy within 30 days. These critical answers can only be rigorously obtained in the setting of controlled animal experiments, and therefore these studies are highly urgent as convalescent plasma use becomes a widespread medical countermeasure against COVID-19 in the coming weeks. The proposed studies will lay the groundwork for evaluating the ?window of opportunity? during which time plasma therapy would be effective post-infection so that plasma infusion may be maximized for clinical benefit as these animal studies will provide answers within a month.